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Vol. 54, Issue 2, 247-264, June 2002
-Aminobutyric AcidB Receptors: Structure and Function
Department of Pharmacology, Medical School, University of
Birmingham, Edgbaston, United Kingdom (N.G.B.); Pharmacenter,
University of Basel, Basel, Switzerland (B.B.); Nervous System
Research, Novartis Pharma, Basel, Switzerland (W.F.); Department of
Pharmacology and Toxicology, University of Texas Medical Branch,
Galveston, Texas (J.P.G.); Millennium Pharmaceuticals, Granta Park,
Great Abington, United Kingdom (F.M.); Department of Experimental
Medicine, Pharmacology and Toxicology, University of Genoa, Genoa,
Italy (M.R.); Laboratory of Genetics, National Institute of Mental
Health, Bethesda, Maryland (T.I.B.); and Department of Pharmacology,
Toxicology and Therapeutics, Kansas University School of Medicine,
Kansas City, Kansas (S.J.E.)
I. Introduction
II. 
-Aminobutyric AcidB Receptor Structure
III. -Aminobutyric AcidB Receptor Effector
Mechanisms
A. Adenylate Cyclase
B. Ion Channels
IV. -Aminobutyric AcidB Receptor Subtypes
V. -Aminobutyric AcidB Receptor Distribution
A. Central Nervous System
B. Peripheral Organs and Tissues
VI. -Aminobutyric AcidB Receptor-Mediated Responses
A. 
-Aminobutyric AcidB Receptor Agonists
1. Antispasticity.
2. Antinociceptive.
3. Suppression of Drug Craving.
4. Miscellaneous Actions.
B. -Aminobutyric AcidB Receptor Antagonists
VII. Conclusions
References
The -aminobutyric acidB
(GABAB) receptor was first demonstrated on presynaptic
terminals where it serves as an autoreceptor and also as a
heteroreceptor to influence transmitter release by suppressing neuronal
Ca2+ conductance. Subsequent studies showed the presence of
the receptor on postsynaptic neurones where activation produces an
increase in membrane K+ conductance and associated neuronal
hyperpolarization. (
)-Baclofen is a highly selective agonist for
GABAB receptors, whereas the established GABAA
receptor antagonists, bicuculline and picrotoxin, do not block
GABAB receptors. The receptor is
Gi/Go protein-coupled with mixed effects on
adenylate cyclase activity. The receptor comprises a heterodimer with
similar subunits currently designated 1 and 2. These subunits are
coupled via coiled-coil domains at their C termini. The evidence for
splice variants is critically reviewed. Thus far, no unique
pharmacological or functional properties have been assigned to either
subunit or the variants. The emergence of high-affinity antagonists for
GABAB receptors has enabled a synaptic role to be
established. However, the antagonists have generally failed to
establish the existence of pharmacologically distinct receptor types
within the GABAB receptor class. The advent of
GABAB1 knockout mice has also failed to provide support for multiple receptor types.
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